Apixaban for Intrahepatic Non Cirrhotic Portal Hypertension

Korábbi kezelés

• Myeloproliferative disease treated with aspirin to prevent vascular events, paroxysmal nocturnal hemoglobinuria.
• Concomitant treatment with any other anticoagulant agent unless when bridging from one to the other is performed
• Transjugular intrahepatic portosystemic shunt (TIPSS) or surgical portosystemic shunt
• Patient who underwent liver transplantation less than 3 years before screening
• Concomitant use of potent inhibitors of CYP3A4 or P-gp. In case of moderate interactions with apixaban (for example, immunosuppressive treatment), the dose of CYP3A4 inhibitor will be adapted according to its plasmatic level in the study patient.

Más betegség

• Complete thrombosis of superior mesenteric vein and/or inferior mesenteric vein
• Complete portal vein thrombosis or portal cavernoma
• Recent (<6 months) partial portal venous system thrombosis
• Disease at high risk of bleeding (except for portal hypertension)
• Active clinically significant bleeding:. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities.
• Hepatitis C with detectable HCV RNA at inclusion
• Mandatory indication to aspirin or other antiplatelet agents including P2Y12 receptor antagonists according to guidelines of the American Heart Association
• Specific causes of portal hypertension or specific vascular liver diseases: history of bone marrow transplantation, Budd-Chiari syndrome / hepatic venous outflow obstruction, hepatic schistosomiasis diagnosed on liver biopsy (an isolated positive serology is not an exclusion criterion), cardiac failure, Fontan surgery, Abernethy syndrome, Hereditary hemorrhagic telangiectasia, chronic cholestatic diseases, liver infiltration by tumor cells
• Hypersensitivity to the active substance or to any of the excipients including lactose.

Laborértékek

• Platelet < 40000/mm3, or prothrombin index <40% in the absence of anti-vitamin K or Factor V < 40% or Fibrinogen < 1.0g/L
• Creatinine clearance < 30 mL/min
• Positive HBs Ag, except patients with HBeAg-negative chronic HBV infection, previously termed 'inactive carriers' [characterised by the presence of serum antibodies to HBeAg (anti-HBe), undetectable or low (<2,000 IU/mL) HBV DNA levels and normal serum ALT levels] that can be included
• Severe hepatic impairment or significant active liver injury (serum ALT level > 5 times the upper limit of normal values)

Egyéb

• Ongoing oestroprogestative contraception
• Pregnant or breastfeeding women
• Mandatory indication or contraindication for anticoagulation according to guidelines of the American college of chest physicians
• Participation in another interventional trial
• Alcohol intake >210 g/week for men and 140 g/week for women
• Life expectancy <12 months
• Patients unable to give consent (under guardianship or curatorship)
• No written informed consent for participation in the study
• No coverage for medical insurance

• 18 and ≤ 90 year old male and female patients,
• For child-bearing aged women, contraception using progestatives, or intrauterine device or mechanical contraception
• Adequate prophylaxis against variceal bleeding according to EASL (European association for the study of the liver) guidelines
• Intrahepatic non cirrhotic portal hypertension (INCPH), defined according to the recent VALDIG workshop (Feb. 2017, Ascona, Italy) as having one of the following simultaneous associations:
  • absence of cirrhosis on an adequate liver biopsy, and one or more signs specific for portal hypertension
  • absence of cirrhosis on an adequate liver biopsy, and one or more signs not specific for portal hypertension and one or more histological signs for INCPH
  • in the absence of adequate liver biopsy, 2 reliable liver stiffness values determined using transient elastography (Fibroscan) < 10 kPa and one or more signs specific for portal hypertension